Purinone derivatives typified by 6-amino-9-[(3R)-1-(2-butynoyl)-3-pyrrolidinyl]-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one (hereinafter sometimes abbreviated as the present compound) have Btk inhibitory activity and are known to be medicaments useful as prophylactic and/or therapeutic agents for B-cell lymphoma and the like (see PTL 1 or 2).
In order to provide the present compound as an active pharmaceutical ingredient, various production methods have been studied. For example, a method for producing the present compound is known, as disclosed in Examples 1 to 9 of PTL 2 (hereinafter sometimes abbreviated as the well-known production method). However, the well-known production method poses four problems as described below. Namely, it has been found that there are problems such that (1) the starting material, 4,6-dichloro-5-nitropyrimidine is potentially explosive; (2) the synthesis is expensive due to tert-butyl (3R)-3-aminopyrrolidine-1-carboxylate, which is an expensive raw material used at an initial stage of the synthesis route; (3) the molecular efficiency is low due to dibenzylamine used as a raw material for introducing an amino group; and (4) in Ullmann condensation using p-phenoxyphenylboric acid during synthesis, a reduction in the reaction yield is observed as the synthesis of the present compound increases. As the well-known production method has such problems, it caused concern that when the present compound was produced in an industrial production scale, the synthesis was expensive and the reaction yield was decreased. Therefore, there is a need for a method for producing the present compound which solves the problems accompanying the well-known production method, allows inexpensive synthesis, has high reaction yield and is suitable for an industrial production scale that can stably supply the present compound.